Various compounds have been proposed as a drug for the treatment of respiratory diseases, such as a vasodilator, a cerebral circulation ameliorator and a drug for the treatment of angina and the like. In this connection, reference may be made to, for example, European Patent No. 0061673 (corresponding to U.S. Pat. No. 4,456,757, U.S. Pat. No. 4,560,755, U.S. Pat. No. 4,525,589, Japanese Patent Application Laid-Open Specification No. 57-156463, Japanese Patent Application Laid-Open Specification No. 57-200366, Japanese Patent Application Laid-Open Specification No. 58-121278, and Japanese Patent Application Laid-Open Specification No. 58-121279), European Patent No. 0109023 (corresponding to U.S. Pat. No. 4,634,770, U.S. Pat. No. 4,709,023, Japanese Patent Application Laid-Open Specification No. 59-93054, and Japanese Patent Application Laid-Open Specification No. 60-81168), U.S. Pat. No. 4,678,783 (corresponding to Japanese Patent Application Laid-Open Specification No. 61-152658 and Japanese Patent Application Laid-Open Specification No. 61-227581), U.S. Pat. No. 4,798,897 (corresponding to Japanese Patent Application Laid-Open Specification No. 62-103066 and Japanese Patent Application Laid-Open Specification No. 62-111981), Journal of Medicinal Chemistry, 32, 42-50 (1989), Agents Actions 28 (3-4), 173-184 (1989), and Pharmacology, 37 (3), 187-194 (1988).
In Japanese Patent Application Laid-Open Specification No. 2-184673, sulfonamides were proposed as a drug for the treatment of respiratory diseases. In Japanese Patent Application Laid-Open Specification Nos. 2-073067 and 2-073068, quinolines and isoquinolines were proposed as a drug for the prevention and treatment of respiratory diseases.
It is known in the art that N-(2-aminoethyl)-N-hexyl-5-isoquinolinesulfonamide and 1-(5-isoquinolinesulfonyl)-3-aminopiperidine disclosed in U.S. Pat. No. 4,798,897 and N-(2-guanidinoethyl)-5-isoquinolinesulfonamides disclosed in Agents Actions, vol. 28, No. 3-4, pp 173-184 (1989), Pharmacology, vol. 37, No. 3, pp 187-194 (1988) and European Patent No. 0109023 have not only a vasodilating effect but also a bronchodilating effect. It is also known in the art that N-[2-3,4-methylenedioxybenzylamino)ethyl]-8-chloro-5-quinolinesulfonamides have a brochodilating effect. However, the vasodilating and bronchodilating effects of the above compounds are not satisfactory.
Bronchodilators, such as xanthine type medicines and .beta.-receptor stimulants, are widely used as a clinical, therapeutic agent for the treatment of respiratory diseases, such as asthma. As a representative example of the xanthine type medicines, aminophylline can be mentioned. Further, as a representative example of the .beta.-receptor stimulants, isoproterenol can be mentioned However, these xanthine type medicines and .beta.-receptor stimulants have side effects on the heart and the like, and an intractable asthma which is not remitted by these medicines has emerged. Therefore, these medicines do not always satisfy the demand of clinicians.
In these situations, the present inventors have made extensive and intensive studies with a view toward developing a drug which is more useful for prevention and treatment of respiratory diseases, such as asthma. As a result, it has been found that a specific substituted sulfonamide derivative, in which the S atom of a sulfonamide moiety has, bonded thereto, a quinolyl group, an isoquinolyl group, a benzothiazolyl group or a quinazolin-4-on group and the N atom of the sulfonamide moiety has, bonded thereto via a methylene group or an alkylene group, a piperazinyl group or a homopiperazinyl group, and an acid addition salt thereof, have strong bronchodilating activity. Based on this finding, the present invention has been completed.
Accordingly, it is an object of the present invention to provide a substituted sulfonamide derivative or an acid addition salt thereof which has an excellent activity to inhibit bronchoconstriction so that it is useful as an active ingredient of a drug for the prevention and treatment of respiratory diseases, such as asthma.
It is another object of the present invention to provide a pharmaceutical composition comprising the above-mentioned sulfonamide derivative or acid addition salt thereof as an active ingredient, which has excellent bronchoconstriction inhibiting activity so that it is useful as a drug for the prevention and treatment of respiratory diseases, such as asthma.
The foregoing and other objects, features and advantages of the present invention will be apparent from the following detailed description and appended claims .